The aim of this study was to investigate the infection process of M. graminicola and the defence mechanisms related to active oxygen species (AOS) in five French wheat cultivars. These cultivars exhibited various resistant levels to M. graminicola infection: Maxyl, Caphorn and Gen11 are susceptible cultivars, whereas Capnor and Gen23 show high levels of quantitative resistances. In addition, Capnor, Gen23 and Gen11 are tolerant cultivars, i.e., their yield performance was less affected by infection compared to non-tolerant cultivars. Cultivars were inoculated with the IPO323 reference M. graminicola strain. First wheat leaves were collected 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days after inoculation. The cytological and antioxidant response of the cultivars were both studied over the whole time course. Although infection occurred mainly through stomata, direct penetration attempts were also scored. Moreover, papilla formation turned out to be very rare. Assays for changes in peroxydase (PO), glutathione-S-transferase (GST) and lipoxygenase (LOX) activities allowed us to compare their levels in the five French wheat cultivars regarding to their resistance and/or tolerance towards M. graminicola infection. PO and GST were correlated to necrosis probably as a consequence of detoxification and LOX was related to some of the germination process steps. We also showed that significant differences for several biochemical parameters exist between the studied cultivars in non inoculated conditions but these differences were less important in the presence of the fungus.